Co-infected Individuals Research Articles

HIV/AIDS and HBV co-infection with optimal control strategies and cost-effectiveness analyses using integer order model

Hepatitis B virus (HBV) and HIV/AIDS co-infection is a common infectious disease that has been spreading through different nations in the world. The main objective of the study is to minimize the number of HBV and HIV co-infected individuals in the community and the cost incurred to the effort applied towards protection and treatment control strategies. In this study, a novel HBV and HIV/AIDS co-infection model has been formulated and analyzed to investigate the effects of protection and treatment control strategies on the spreading dynamics of the HBV and HIV/AIDS co-infection in the community. In the qualitative analyses we have computed all the models disease-free equilibrium points, all the models effective reproduction numbers and unique endemic equilibrium points, we have proved the two sub-models disease-free equilibrium points are locally as well as globally asymptotically stable whenever their associated effective reproduction numbers are less than one. In our understanding no one is formulated and analyzed the HBV and HIV/AIDS co-infection model with optimal control and cost-effective analyses so that we have formulated the associated optimal control problem and carried out the optimal control analysis on the HBV and HIV/AIDS co-infection model by implementing the Pontryagin’s minimum principle. Numerical simulations with various combinations of the control efforts implemented are then carried out to investigate the impacts of protection and treatments to tackle the HBV and HIV/AIDS co-infection diseases spreading in the community. Finally, we also carried out cost-effectiveness analysis for the implemented control strategies. From the findings of the numerical simulations we observed that implementing all the proposed controlling strategies simultaneously has fundamental impact to minimize and control the HBV and HIV/AIDS co-infection spreading in the community but cost-effectiveness analysis proved that implemented strategy 4 (implemented the HIV protection and HBV treatment controls simultaneously) is the most cost-effective strategy as compared with all other implemented strategies and we recommend for the health stake holders and policy makers to implement this strategy to tackle the HBV and HIV/AIDS co-infection spreading problem in the community.

P-781. The Impact of Hepatitis B Virus Infection on the Management of Latent Tuberculosis Infection in Northern California, 2010-2022

Abstract Background Tuberculosis (TB) and hepatitis B virus (HBV) infection affect similar at-risk populations. However, there is limited data on how co-infection may influence clinicians’ decision to offer TB preventative treatment (TPT) over concern for hepatotoxicity. We compared TPT by HBV status, and determined factors associated with TPT initiation among HBV-infected persons at a community health center in Northern California serving a large non-U.S.-born Asian population. Methods We extracted electronic health record data for all persons aged ≥18 years old with latent TB infection (LTBI), defined by a positive tuberculin skin test or interferon-gamma release assay in the absence of a TB disease diagnosis from 2010-2022. HBV infection was defined by a single positive HBV DNA or HBV surface antigen assay. We conducted multivariate logistic regression to explore the impact of (a) HBV status and (b) clinical and demographic variables on TPT initiation. We also examined how these factors changed when Rifampin (RIF) usage for TPT increased at this community health center after 2014. Results A total of 11,711 persons had LTBI and 5,530 had HBV. Of all persons with LTBI, 833 (9.0%) of those tested for HBV had a co-infection including 41 (4.9%) on HBV antiviral treatment; while 34% of all HBV-infected persons screened for TB had LTBI. Adjusting for demographics and time period, TPT was significantly lower among those with co-infection than those without (43.5% versus 47.4%, adjusted Odds Ratio (aOR) 0.76, 95% Confidence Interval (CI) 0.66 – 0.88, p< 0.01). Among those with co-infection, increasing age (50-64, ≥65 years), and elevated alanine transaminase (ALT) levels were associated with decreased likelihood of TPT (Table 1). Treatment of co-infected individuals was significantly higher after 2014 when RIF prescribing increased (aOR 2.76, 95% CI 1.81-4.2); however, age over 65 was still associated with decreased TPT prescription (aOR 0.36, 95% 0.19 – 0.67, p < 0.01). Conclusion HBV-LTBI co-infection was associated with reduced odds of TPT. Increased use of Rifamycin based regimens and further guidance on TPT and monitoring of older individuals and persons with elevated ALT levels may be needed to improve TB prevention efforts among HBV-LTBI co-infected persons. Disclosures Robert J. Wong, MD, MS, Durect Corporation: Grant/Research Support|Exact Sciences: Grant/Research Support|Gilead Sciences: Grant/Research Support|Thera Technologies: Grant/Research Support

Parasitological and clinical correlates of Plasmodium–Schistosoma mansoni co-infection and its determinants among Plasmodium-infected patients in the Wolaita Zone, South Ethiopia regional state

BackgroundMalaria and schistosomiasis are among the most important parasitic diseases with overlapping geographical distribution in Ethiopia. The objective of this study, therefore, was to assess parasitological and clinical correlates and determinants of co-infection among malaria patients.MethodsA health facility-based comparative cross-sectional study was conducted among malaria patients attending public health facilities in Damot Woyide district, Wolaita zone, South Ethiopia regional state, from December 2020 to June 2021. A total of 246 (123 Plasmodium-only and 123 Plasmodium–Schistosoma mansoni co-infected) study participants were sampled consecutively. A pre-tested structured questionnaire was used to collect data on demographic and risk factors. Detection and quantification of Schistosoma mansoni ova and malaria parasites were done with the Kato–Katz technique and blood film, respectively. Determination of hematological and biochemical parameters was done by the aLCose®HemoGo test system and the Cobas C 311 chemistry analyzer, respectively.ResultsThe prevalence of Plasmodium–Schistosoma mansoni co-infection was 18.2%. Plasmodium–Schistosoma mansoni co-infected with a heavy intensity of Schistosoma mansoni had the highest parasitemia and was also significantly associated with malaria attack. In addition, anemia was associated with the presence of Plasmodium–Schistosoma mansoni co-infection. Schistosoma mansoni co-infection among malaria patients significantly increased mean Plasmodium density, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, direct bilirubin, and total protein. Hemoglobin and hematocrit were significantly lower among co-infected individuals. On multivariate analysis, being male (AOR=3.03, CI: 1.56-5.91,p=0.001), being in the 6-15 years age group (AOR = 5.85, CI: 2.45–13.93,p=0.00), the presence of stream (AOR = 4.1, CI: 1.65–10.15,p=0.002), having a water body distance of less than 1,000 m (AOR=2.33, CI: 1.23–4.41,p=0.009), and presence of irrigation practice (AOR= 3.24, CI: 1.69–6.18,p=0.00) were found to be significant risk factors of co-infection.ConclusionMalaria attack and level of parasitemia were associated with the intensity of concurrent Schistosoma mansoni infection. Co-infection results in the change of Plasmodium density, hematological, and biochemical parameters in malaria patients.

Analyses of blood-derived host biomarkers for pulmonary tuberculosis diagnosis in human immunodeficiency virus co-infected individuals in sub-Saharan Africa: a systematic review and meta-analysis

ObjectiveOur objective was to conduct a review of host blood-derived biomarkers as potential diagnostic targets for pulmonary TB and as alternative tests to identify active tuberculosis in HIV co-infected individuals.MethodsA systematic review and meta-analysis of host blood-derived biomarkers with potential for diagnosis of active tuberculosis in HIV co-infected individuals was conducted. Cochrane Library, Embase, MEDLINE, PubMed and Web of Science databases were searched up to 7 November 2023. A hierarchical summary receiver operating characteristic (HSROC) model was used to evaluate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) of the following potential biomarkers: C-reactive protein (CRP), Interferon gamma induced protein-10 (IP-10), Neopterin, IGRA, Kynurenine to tryptophan (K/T) ratio and use of different panels of combined biomarkers; including 5 biomarker panel (IL-6, INF-y, MIG, CRP, and IL-18), 4 biomarker panel (IL-6, IL-21, INF-y, IL-1a), 6 biomarker panel (APO-ACIII, CXCL1, CXCL9, CCL8, CCL-1, and CD56), and 9 biomarker panel (Alpha-2-macroglobulin, fibrinogen, CRP, MMP-a, transthyretin, complement factor H, INF-y, IP-10, and TNF-α).ResultsTwenty-three studies were included. The pooled sensitivity of CRP, IP-10, Neopterin, combined biomarker signatures, IGRA and K/T ratio were 77% (60–88), 79% (72 - 84), 82% (43–96), 78% (64–88), 71% (65–76), 95% (90–98), respectively and the pooled specificity were 90% (80–96), 82% (59–93), 42% (22–66), 85% (73–92), 33% (18–54), and 95% (82–99), respectively.ConclusionCRP, IP-10, K/T ratio and the panels of multiple combined biomarkers that include the following cytokines, chemokines, and acute phase proteins IL-6, INF-y, MIG, CRP, IL-18, IL-21, IL-1a, APO-ACIII, CXCL1, CXCL9, CCL8, CCL-1, CD56, Alpha-2-macroglobulin, fibrinogen, MMP-a, transthyretin, complement factor H, IP-10, and TNF-α are potential blood biomarkers that can aid TB diagnosis in HIV co-infected individuals.

Risky sexual practice and associated factors among antiretroviral therapy attendees in public health facilities, Wolaita Zone, South Ethiopia: a multi-center cross-sectional study.

The majority of people living with Human Immunodeficiency Virus (HIV) are in low- and middle-income countries, particularly in sub-Saharan Africa. Increased risky sexual practice puts people living with the human immune virus at higher risk of acquiring sexually transmitted infections other than the human immune virus and unplanned pregnancies. Sexually transmitted infections, particularly viral hepatitis (B and C), significantly impair antiretroviral therapy and the clinical outcome of the co-infected individual, leading to increased morbidity and mortality. The purpose of this study was to investigate the prevalence of risky sexual practices among antiretroviral therapy (ART) attendees in public health facilities within the Wolaita Zone of South Ethiopia. From September to October 2023, a facility-based cross-sectional study was conducted among adult people living with HIV on ART in the Wolaita zone. Data was collected through a pretested and structured questionnaire. Six diploma nurses were trained to collect data. Systematic sampling techniques were used to select a total of 398 ART patients. Data were collected by Open Data Kit (ODK) and analyzed with SPSS Version 25. Binary and multiple logistic regression analyses were used. All the variables with a P-value of 0.25 associated with risky sexual practices are considered candidate variables. Multicollinearity was checked. The fitness of the model was tested by the Hosmer-Lemshow goodness of fit test. Finally, statistical significance was declared at a p-value of 0.05. A total of 398 respondents took part in this study. The prevalence of risky sexual practices in the past six months was 174 (43.7%) at 95% of the CI (38.9-48.7). The result of multiple logistic regression analysis showed that not disclosing HIV status (AOR = 1.8, 95% CI: 1.1-3.31), alcohol drinking (AOR = 3.1, 95% CI: 1.66-0.023), and poor social support (AOR = 1.9, 95% CI: 1.75-3.9) were statistically significantly associated with risky sexual practices. This study revealed that the risky sexual practice among ART clients was high and disclosure status, social support, and alcohol use were factors associated with risky sexual practice. The governmental and non-governmental bodies have to strengthen social support for ART clients, disclosure status for ART clients, and counseling to avoid alcohol.

A two-strain COVID-19 co-infection model with strain 1 vaccination

COVID-19 has caused substantial morbidity and mortality worldwide. Previous models of strain 1 vaccination with re-infection when vaccinated, as well as infection with strain 2 did not consider co-infected classes. To fill this gap, a two co-circulating COVID-19 strains model with strain 1 vaccination, and co-infected is formulated and theoretically analyzed. Sufficient conditions for the stability of the disease-free equilibrium and single-strain 1 and -strain 2 endemic equilibria are obtained. Results show as expected that (1) co-infected classes play a role in the transmission dynamics of the disease (2) a high efficacy vaccine could effectively help mitigate the spread of co-infection with both strain 1 and 2 compared to the low-efficacy vaccine. Sensitivity analysis reveals that the main drivers of the effective reproduction number Re are primarily the effective contact rate for strain 2 (β2), the strain 2 recovery rate (τ2), and the vaccine efficacy or infection reduction due to the vaccine (η). Thus, implementing intervention measures to mitigate the spread of COVID-19 should not ignore the co-infected individuals who can potentially spread both strains of the disease.

Hepatitis Delta Coinfection Rates and All-Cause Mortality Among Hepatitis B-Infected Veterans in the USA.

Screening for hepatitis D virus (HDV) is recommended for all individuals with hepatitis B virus (HBV) infection. Coinfected individuals experience more severe liver-related outcomes. We determined the HDV testing and coinfection rates and all-cause mortality among those infected with HBV. We used the US Department of Veterans Affairs (VA) healthcare system's national databases to identify individuals with HBV infection. We determined the proportion of individuals referred to gastroenterologists/hepatologists, or infectious diseases providers, and the proportion screened and tested positive for HDV. We calculated the HBV treatment rates, defined as ≥ 3 months of continuous prescription with an approved drug. Finally, we calculated all-cause mortality stratified by HDV coinfection and HBV treatment status. Among 44,951 individuals with at least one positive HBsAg, HBeAg or HBV DNA test, 5964 (13.3%) were screened for HDV (180 [3.0%] tested positive), and 28,291 (62.9%) were referred to gastroenterology/hepatology or infectious diseases. Treatment for HBV was prescribed for 73 (40.5%) of HDV-coinfected and 2425 (41.9%) HDV-uninfected individuals. All-cause mortality rate per 100 person-years was lower among those without HDV coinfection (2.98 for untreated HBV, 2.53 for treated HBV; p < 0.001) compared with those with HDV coinfection (5.14 for untreated HBV, 3.0 for treated HBV; p = 0.02). Kaplan-Meier curves demonstrated a significantly higher mortality among HDV-coinfected individuals who were not treated for HBV (log-rank p < 0.0001). Screening rates for HDV among HBV-infected individuals are suboptimal. While HDV coinfection is associated with higher all-cause mortality, HBV treatment may confer a survival benefit.

Chronic Viral Infections and Hepatic Oncogenesis

Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are major contrib¬utors to chronic liver disease and hepatocellular carcinoma (HCC) worldwide. Discovered in the 1960s and 1980s, these viruses are associated with significant global health burdens. HBV, a member of the He¬padnaviridae family, is a partially double-stranded DNA virus responsible for chronic liver infections that can lead to HCC. Despite the success of HBV vaccination, challenges such as vaccine escape mutants and non-responders persist. HCV, a member of the Flaviviridae family and a positive-sense single-stranded RNA virus, affects millions globally. While direct-acting antivirals (DAAs) can achieve high rates of viral clearance, vaccine development remains hindered by genetic diversity and immune evasion. HDV, the smallest known human virus, relies on HBV for its propagation. It exacerbates liver disease and increases HCC risk, particularly in co-infected individuals. HDV does not integrate into the host genome, suggesting indirect mechanisms of carcinogenesis, potentially through interactions with HBV. Addressing these chal¬lenges requires enhanced vaccination strategies, improved antiviral therapies, and continued research to understand the complex interplay between these viruses and liver cancer development.

Hepatitis B prevalence and risk factors among adults living with HIV in South Africa: a clinic-based cohort study

BackgroundPeople living with HIV (PLHIV) may have concurrent Hepatitis B Virus (HBV) infection, and certain antiretroviral therapies are recommended for HBV-HIV co-infected individuals. Routine screening for Hepatitis B virus may influence management of antiretroviral therapy for PLHIV, but risk factors for co-infection have not been well defined. The objective of this study was to identify risk factors for HBV infection among PLHIV in South Africa.MethodsWe conducted a cross-sectional analysis of a prospective, clinic-based cohort study of adults seeking HIV testing from 2013–2017 in Umlazi township, South Africa. Patients newly diagnosed with HIV were enrolled and subsequently tested for Hepatitis B surface antigen positive (HBsAg +). We used a Poisson linear regression model to assess which factors, pertaining to sociodemographic status, medical history, clinical symptoms, mental health were associated with HBV.ResultsAmong 3,105 PLHIV participants in South Africa, 6% were positive for HBV. Males had a higher HBV prevalence (10.4%) than females (5.2%). Within the HBV-positive group, the mean age was 33.2 years, with 38.3% females and 43.9% having completed high school or higher. About 39.9% reported alcohol use, 24.7% had a smoking history, and 8.3% reported substance use in the past year. Older participants born before 1995, when routine infant HBV vaccination was introduced, were more likely to have HBV. In multivariable analyses, smoking history increased HBV risk in females (aPR = 2.58; 95% CI 1.47–2.52), while alcohol use decreased HBV risk in males (aPR = 0.36; 95% CI 0.19–0.70).ConclusionsIn a South African cohort, roughly one in 16 PLHIV had HBV co-infection, and this rate was higher in males. The most prominent risk factors for HBV infection in PLHIV were alcohol use, higher income, and smoking history, which may help inform targeted treatment and prevention strategies. Creating HBV-specific screening and prevention strategies for PLHIV may be useful for reducing HBV infections.

Concurrent TB and HIV therapies effectively control clinical reactivation of TB during co-infection but fail to eliminate chronic immune activation.

The majority of Human Immunodeficiency Virus (HIV) negative individuals exposed to Mycobacterium tuberculosis (Mtb) control the bacillary infection as latent TB infection (LTBI). Co-infection with HIV, however, drastically increases the risk to progression to tuberculosis (TB) disease. TB is therefore the leading cause of death in people living with HIV (PLWH) globally. Combinatorial antiretroviral therapy (cART) is the cornerstone of HIV care in humans and reduces the risk of reactivation of LTBI. However, the immune control of Mtb infection is not fully restored by cART as indicated by higher incidence of TB in PLWH despite cART. In the macaque model of co-infection, skewed pulmonary CD4+ TEM responses persist, and new TB lesions form despite cART treatment. We hypothesized that regimens that concurrently administer anti-TB therapy and cART would significantly reduce TB in co-infected macaques than cART alone, resulting in superior bacterial control, mitigation of persistent inflammation and lasting protective immunity. We studied components of TB immunity that remain impaired after cART in the lung compartment, versus those that are restored by concurrent 3 months of once weekly isoniazid and rifapentine (3HP) and cART in the rhesus macaque (RM) model of LTBI and Simian Immunodeficiency Virus (SIV) co-infection. Concurrent administration of cART + 3HP did improve clinical and microbiological attributes of Mtb/SIV co-infection compared to cART-naïve or -untreated RMs. While RMs in the cART + 3HP group exhibited significantly lower granuloma volumes after treatment, they, however, continued to harbor caseous granulomas with increased FDG uptake. cART only partially restores the constitution of CD4 + T cells to the lung compartment in co-infected macaques. Concurrent therapy did not further enhance the frequency of reconstituted CD4+ T cells in BAL and lung of Mtb/SIV co-infected RMs compared to cART, and treated animals continued to display incomplete reconstitution to the lung. Furthermore, the reconstituted CD4+ T cells in BAL and lung of cART + 3HP treated RMs exhibited an increased frequencies of activated, exhausted and inflamed phenotype compared to LTBI RMs. cART + 3HP failed to restore the effector memory CD4+ T cell population that was significantly reduced in pulmonary compartment post SIV co-infection. Concurrent therapy was associated with the induction of Type I IFN transcriptional signatures and led to increased Mtb-specific TH1/TH17 responses correlated with protection, but decreased Mtb-specific TNFa responses, which could have a detrimental impact on long term protection. Our results suggest the mechanisms by which Mtb/HIV co-infected individuals remain at risk for progression due to subsequent infections or reactivation due of persisting defects in pulmonary T cell responses. By identifying lung-specific immune components in this model, it is possible to pinpoint the pathways that can be targeted for host-directed adjunctive therapies for TB/HIV co-infection.

Co-infection dynamics of B. afzelii and TBEV in C3H mice: insights and implications for future research.

Ticks are important vectors of disease, particularly in the context of One Health, where tick-borne diseases (TBDs) are increasingly prevalent worldwide. TBDs often involve co-infections, where multiple pathogens co-exist in a single host. Patients with chronic Lyme disease often have co-infections with other bacteria or parasites. This study aimed to create a co-infection model with Borrelia afzelii and tick-borne encephalitis virus (TBEV) in C3H mice and to evaluate symptoms, mortality, and pathogen level compared to single infections. Successful co-infection of C3H mice with B. afzelii and TBEV was achieved. Outcomes varied, depending on the timing of infection. When TBEV infection followed B. afzelii infection by 9 days, TBEV symptoms worsened and virus levels increased. Conversely, mice infected 21 days apart with TBEV showed milder symptoms and lower mortality. Simultaneous infection resulted in mild symptoms and no deaths. However, our model did not effectively infect ticks with TBEV, possibly due to suboptimal dosing, highlighting the challenges of replicating natural conditions. Understanding the consequences of co-infection is crucial, given the increasing prevalence of TBD. Co-infected individuals may experience exacerbated symptoms, highlighting the need for a comprehensive understanding through refined animal models. This study advances knowledge of TBD and highlights the importance of exploring co-infection dynamics in host-pathogen interactions.

Elevated Inflammation Associated with Markers of Neutrophil Function and Gastrointestinal Disruption in Pilot Study of Plasmodium fragile Co-Infection of ART-Treated SIVmac239+ Rhesus Macaques.

Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Moreover, there is limited data available on the impact of Plasmodium co-infection on antiretroviral (ART)-treated HIV infection. Here, we used the rhesus macaque (RM) model to conduct a pilot study to establish a model of Plasmodium fragile co-infection during ART-treated simian immunodeficiency virus (SIV) infection, and to begin to characterize the immunopathogenic effect of co-infection in the context of ART. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VLs) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was also associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in the neutrophil functionality during co-infection. Finally, we characterized the levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these pilot data verify the utility of using the RM model to examine ART-treated SIV/P. fragile co-infection, and indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.

Prevalence and predictors of hepatic steatosis among HIV patients with and without chronic hepatitis C

Background and purpose of the studyHepatic steatosis (HS) is a common and important histologic finding in patients with chronic hepatitis C virus (HCV) infection. However, little is known about this finding in HCV patients co-infected with human immunodeficiency virus (HIV).Purpose of the studyTo evaluate the prevalence and predictors of HS among HIV patients with and without HCV.MethodsA cross-sectional including 47 HIV mono-infected and 50 HIV/HCV patients. Detailed demographic, laboratory and clinical data were collected. A transient elastography (TE) examination with the controlled attenuation parameter (CAP) was performed for all patients. Steatosis was scored on a scale from 0 to 3 according to the percentage of steatosis involving hepatocytes.ResultsHS was detected in 18 /50 (36%) HIV/HCV co-infected patients and 22 /47 (46.8%) HIV mono-infected patients. In addition, HCV mono-infected patients were more likely to have grade 2 steatosis as compared with HIV/HCV co-infected individuals (25.5% vs. 12%). LSM was significantly higher among HIV/HCV co-infected patients (p = 0.003). When dividing HIV/HCV co-infected and HIV mono-infected group according to CAP values. BMI, abdominal wall thickness, and bright liver were significantly associated with SHS (CAP ≥ 238 dB/m) in both groups. Diabetes was only significantly associated with SHS in HIV/HCV co-infected group BMI was the only independent predictor of SHS among the whole group and subgroup analysis.ConclusionThe prevalence of HS was lower in HIV/HCV co-infected patients compared to HIV mono-infected patients; we cannot say that HCV has a protective role against HS in co-infected patients. More fibrosis progression was common in the HIV/HCV co-infected patients.

Investigation of hepatitis B virus mutations associated with immune escape and drug resistance in human immunodeficiency virus-infected patients

Background Co-infection of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) has an impact on high HBV replication and progression to liver cancer. These may lead to cross-resistance of drugs due to therapeutic pressure or liver toxicity. These require continuous monitoring of HBV variants for better diagnosis and treatment strategies. Methods Convenience sampling was used to collect fifty archival sera from Inkosi Albert Luthuli Central Hospital. The Sera were subjected to HBsAg screening using ELISA, DNA extraction, PCR amplification, Sanger sequencing, phylogenetic and mutation analysis. A correlation test was performed to measure the association between polymerase and surface mutations. Results Of the 50 samples, 86% (N= 43/50) were HBsAg positive; 82% (N=41/50) PCR positive and 92% (N=38/41) sequenced. The HBV sequences showed similarity to genotype A (73% [N=19/26]) and (24% [N=7/26]) as genotypes B, C, D, E, F, and G. Prevalence of the mutations in the Surface region was (47% [N=18/38]); including diagnostic failure (K122R and T143S) and vaccines escape mutations (P127T, G145R, S207N, Y200T, E164D, Y206H and L209V). The mutations in the RT was at (36% [N=14/38]) with drug resistance mutations (DRM) at (50% [7/14]). Mutations showed resistance to lamivudine (LMV) at (35% [5/14]), telbivudine (LdT) at (29% [4/14]), (14% [2/14]) for entecavir (ETV) and (21% [3/14]) for adefovir (ADV). One sample had a combination of L180M, M204V, S202K, and M250I mutations. There was no statistical significance between S and RT mutations at P&gt;0.005 and the statistical correlation between RT and SHB mutations was weak at 0.877. Conclusions Our findings highlight the prevalence of HBV genotype A in HIV-infected patients in South Africa. We provide evidence of mutations linked to immune evasion and drug resistance. Mutations have no statistical significance but can have clinical Implication on the diagnosis and treatment of HBV in HBV/HIV co-infected individuals.

HCV Cascade of Care in HIV/HCV Co-Infected Individuals: Missed Opportunities for Micro-Elimination.

People living with HIV-HCV co-infection comprise a target group for HCV-micro-elimination. We conducted an HCV cascade of care (CoC) for HIV-HCV co-infected individuals living in Greece and investigated factors associated with different HCV-CoC stages. We analyzed data from 1213 participants from the Athens Multicenter AIDS Cohort Study. A seven-stage CoC, overall and by subgroup (people who inject drugs (PWID), men having sex with men (MSM), men having sex with women (MSW), and migrants], was constructed, spanning from HCV diagnosis to sustained virologic response (SVR). Logistic/Cox regression models were employed to identify factors associated with passing through each CoC step. Among 1213 anti-HCV-positive individuals, 9.2% died before direct-acting antiviral (DAA) availability. PWID exhibited higher mortality rates than MSM. Of 1101 survivors, 72.2% remained in care and underwent HCV-RNA testing. Migrants and PWID showed the lowest retention rates. HCV-RNA was available for 79.2% of those in care, with 77.8% diagnosed with chronic HCV. Subsequently, 71% initiated DAAs, with individuals with very low CD4 counts (<100 cells/μL) exhibiting lower odds of DAA initiation. SVR testing was available for 203 individuals, with 85.7% achieving SVR. The SVR rates did not differ across risk groups. In 2023, significant gaps and between-group differences persisted in HCV-CoC among HIV-HCV co-infected individuals in Greece.

Colliding Challenges: An Analysis of SARS-CoV-2 Infection in Patients with Pulmonary Tuberculosis versus SARS-CoV-2 Infection Alone.

Background and Objectives: The concurrent occurrence of tuberculosis and COVID-19 coinfection poses significant clinical complexities, warranting a nuanced approach to diagnosis, management, and patient care. Materials and Methods: A retrospective, cross-sectional study was conducted on two groups: one comprising 32 patients with pulmonary TB (PTB) and COVID-19 co-infection, and one including 100 patients with COVID-19 alone. Data was collected from medical records, including patient history, clinical parameters, laboratory, imaging results, and patient outcome. Results: A lower BMI emerges as a significant marker suggesting underlying PTB in patients with SARS-CoV-2 co-infection. Type 2 diabetes mellitus increases the risk of death in PTB-SARS-CoV-2 co-infection. Co-infected patients show lymphocytopenia and higher neutrophil levels, CRP, transaminases, and D-dimer levels. Elevated CRP and ALT levels are linked to increased co-infection likelihood. Certain parameters like SpO2, CRP, ALT, AST, and D-dimer effectively differentiate between co-infected and COVID-19 patients. Platelet-to-lymphocyte ratio is notably higher in co-infected individuals. Lesion severity on imaging is significantly associated with co-infection, highlighting imaging's diagnostic importance. Longer hospital stays are linked to co-infection but not significantly to death risk. Conclusions: Certain clinical and biological factors may serve as potential indicators of PTB co-infection in patients with SARS-CoV-2.

Predictors of quality of life of TB/HIV co-infected patients in the Northern region of Ghana

BackgroundTuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) co-morbidity continues to be a serious worldwide health issue, particularly in Sub-Saharan Africa. Studies on the quality of life (QOL) of TB/HIV co-infected patients guide stakeholders on the delivery of patient-centred healthcare. This study evaluated QOL of TB/HIV co-infected individuals and its contributing factors.MethodsWe conducted a cross-sectional study among TB/HIV co-infected patients, receiving treatment at clinics in the Northern Region of Ghana. Simple random sampling technique was used to select 213 patients from 32 clinics. We gathered information on patients’ QOL using the World Health Organization QOL-HIV BREF assessment tool. At a 5% level of significance, multiple logistic regression analyses were carried out to find correlates of QOL among the patients.ResultsThe mean age of the patients was (38.99 ± 14.00) years with most, 33.3% (71/213) aged 30–39 years. Males constituted 54.9% (117/213). About 30.0% (64/213) of the patients reported a good QOL. Being employed (aOR = 5.23, 95% CI: 1.87 – 14.60), and adhering to treatment (aOR = 6.36, 95% CI: 1.51 – 26.65) were significantly associated with a good QOL. Being depressed (aOR = 0.02, 95% CI: 0.03 – 0.29), stigmatized (aOR = 0.31, 95% CI : 0.11 – 0.84), and not exercising (aOR = 0.28, 95% CI: 0.12 – 0.67) were negatively associated with a good QOL.ConclusionLess than one-third of TB/HIV co-infected patients in the region have good QOL. To guarantee good QOL, modifiable predictors such as patients’ physical activity and medication adherence should be targeted by the National AIDS and TB Control Programs.

Peripheral Neuropathy in Patients with Hepatitis C Infection-Reversibility after HCV Eradication: A Single Center Study.

Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.

Abstract 120: A closer Look at colorectal cancer risk: Insights from the complex relationship of HIV, helminths, and immune responses

Abstract The advent of antiretroviral therapy has markedly increased the survival rates of individuals with human immunodeficiency virus (HIV). However, this demographic, particularly in low-middle-income countries (LMICs) where HIV-helminth co-infections are prevalent, remains susceptible to infections. The intricate interplay between helminth infections and HIV susceptibility, often inducing immunological phenotypes that heighten vulnerability, remains poorly understood. Studies have shown the association between HIV-helminth co-infections and elevated susceptibility to colorectal cancer (CRC), introducing an additional layer of health concerns for this already vulnerable population. This retrospective observational study delves into the profound effects of HIV-helminth co-infections on immune responses, with a specific focus on type 2 T helper (Th2) cell immunomodulation and susceptibility to CRC. Utilizing samples from a master project (n=414), 80 systematically randomized individuals were categorized into uninfected control, HIV-infected only, helminth-infected only, and HIV-helminth co-infected groups. Parasite detection employed the Kato-Katz technique, and serum testing was conducted for helminth-specific antibodies. Serological HIV testing, viral load categorization, white blood cell counts, and differential analyses were performed. Human ProcartaPlex Panel 1 was used for cytokine profiling of immune stimulatory and inhibitory soluble proteins. A significant reduction in B and T lymphocyte attenuator (BTLA) (p=0.049) in helminth infections compared to the control. The association of BTLA with its ligand, herpesvirus entry mediator (HVEM), establishes a direct link between the CD28 and tumor necrosis factor receptor (TNFR) families, triggering wide-ranging and robust immune responses. Subsequently, a notable reduction in CD28 was observed in HIV-infected subjects (p=0.003), followed by helminth-infected and HIV-helminth co-infected individuals (p=0.03) compared to the control. Furthermore, programmed death ligand-2 (PD-L2) expression, a major contributor to alternatively activated macrophage polarization during helminth infections, was significantly increased in the HIV-helminth co-infected group (p = 0.05), favoring a shift towards Th2 immune responses. These observed alterations underscore the complexity of the immunological interplay in co-infected individuals, emphasizing an additional risk factor for colorectal cancer development. This necessitates a comprehensive understanding, providing valuable insights for the development of therapeutic strategies in LMICs and similar settings, addressing the heightened risk of CRC within this population. Citation Format: Botle P. Damane, Thanyani V. Mulaudzi, Sayed S. Kader, Ropo E. Ogunsakin, Pragalathan Naidoo, Zodwa Dlamini, Zilungile L. Mkhize-Kwitshana. A closer Look at colorectal cancer risk: Insights from the complex relationship of HIV, helminths, and immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 120.

The effect of HIV and mpox co-infection on clinical outcomes: Systematic review and meta-analysis.

Co-infection with HIV and mpox is a significant issue for public health because of the potential combined impact on clinical outcomes. However, the existing literature lacks a comprehensive synthesis of the available evidence. The purpose of this meta-analysis is to provide insight into the impact of HIV and mpox co-infection on clinical outcomes. We systematically searched major electronic databases (PubMed, Embase, Cochrane Central, and Web of Science) for pertinent studies published up to June 2023. Included were studies that described the clinical outcomes of people who had both mpox and HIV. We performed the analysis using OpenMeta and STATA 17 software. With an overall number of participants of 35 207, 21 studies that met the inclusion criteria were considered. The greatest number of the studies (n = 10) were cohort designs, with three being cross-sectional and eight being case series studies. The meta-analysis found that people who had both HIV and mpox had a higher hospitalization rate than those who only had mpox (odds ratio [OR] 1.848; 95% confidence interval [CI] 0.918-3.719, p = 0.085, I2 = 60.19%, p = 0.020). Furthermore, co-infected patients had higher mortality rates than those who did not have HIV co-infection (OR 3.887; 95% CI 2.272-6.650, p < 0.001). Meta-regression analysis showed that CD4 levels can significantly predict the risk of hospitalization (p = 0.016) and death (p = 0.031). HIV causes immunosuppression, making it difficult for the body to mount an effective immune response against pathogens such as mpox. Individuals who are co-infected are at a higher risk of severe disease and death, according to our findings. Although hospitalization rates did not differ significantly between the two groups, it is critical to prioritize interventions and improve management strategies tailored specifically for people living with HIV. This meta-analysis provides substantial evidence that HIV and mpox co-infection has a negative impact on clinical outcomes. Co-infected individuals had higher hospitalization and significantly higher mortality rates. These findings highlight the significance of early diagnosis, prompt treatment initiation, and effective management strategies for people living with HIV and mpox.